The aims of this proposal are 1) to establish the effectiveness of five putative dietary inhibitors against three carcinogens in rainbow trout, and 2) to determine their mechanisms of action. Trout will be fed diets containing Beta-naphthoflavone (Beta-NF), idole-3-carbinol (I-3-C), disulfiram, Edi Pro A soybean protein concentrate, or garlic extract either after, or before and during, carcinogen exposure. The carcinogens will be aflatoxin B1 (AFB1), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), or N-nitrosodiethylamine (DEN). These carcinogens differ in characteristics of metabolism, DNA adducts, and repair, and induce tumors in trout at one or more sites including liver, kidney, thyroid, stomach and gonad. Tumor incidences will be determined at 12 months. Compounds which inhibit when given prior to and with carcinogen will be examined for specific effects on initiation processes. These include effects on overall carcinogen pharmacokinetic distribution and excretion, metabolite patterns, DNA adduct formation in target organs, and leukocyte sister chromatid exchange following a single in vivo exposure to procarcinogen (AFB1) or direct carcinogen (MNNG). For hepatocarcinogens, in vitro studies in isolated hepatocytes will examine cellular effects of dietary inhibitor and in vitro addition of inhibitor on procarcinogen metabolism, detoxication, and DNA adduct formation. Compounds which inhibit when fed after the carcinogen will be examined for specific post-initiation effects. These include effects on general growth and target cell proliferation, DNA repair in vivo, competence for unscheduled DNA synthesis (repair) in vitro in isolated hepatocytes, and progression of transplanted tumors in in-bred trout. Some compounds may show initiation as well as post-initiation effects, either inhibitory or promotional, and these will also be studied. Three of the components under study here (1-3-C, garlic, soybean protein) are common in the human diet and it is important to understand their possible significance in human carcinogenesis. These studies complement those in other vertebrate models in examining effectiveness and mechanisms for these and other components. Inhibitors which are consistent in protection and mechanisms without significan noxious behavior may play a furure role in chemoprevention in man; promoting compounds identified by such studies may warrant deliberate avoidance.